Sequential therapy with allogeneic HCT in patients aged ≥70 years with active AML: a single-center retrospective...

Patients ≥70 years with relapsed/refractory acute myeloid leukemia (AML) have an extremely poor prognosis. We adopted a sequential therapy approach, aiming to proceed directly to allogeneic hematopoietic cell transplantation (HCT) despite active disease. We analyzed results of all consecutive patients aged over 70 years and diagnosed with primary refractory/ relapsed AML who underwent HCT with sequential therapy approach (FITCy regimen) in the Tel Aviv Sourasky Medical Center. Fifty-one patients (median age 72 years; primary refractory N=42; relapse N=9). Median follow-up was 35 (range, 12-91) months. Incidences of overall and grade 3-4 acute graft-versus-host disease (GVHD) were 39.2% (95% confidence interval [CI]: 25.6-52.8), and 5.9% (95% CI: 0.0-12.5), respectively. Incidences of overall and moderate-severe chronic GVHD were 40.0% (95% CI: 25.7-57.1) and 29.4% (95% CI: 13.2-46.9), respectively. Non-relapse mortality at 3 years was 36% (95% CI: 22- 49). Forty-two of 51 patients (82.4%) had CR on day +30 post HCT. Relapse incidence at 3 years was 27.8% (95% CI: 14.3-41.2). GVHD-free relapse-free and overall survival (OS) at 3-years were 30% (95% CI: 19-47) and 31% (95% CI: 17-55), respectively. Multivariable analysis showed that worse European LeukemiaNet 2022 score, relapsed AML (vs. primary-refractory), not receiving ATG, and lower albumin prior to conditioning, were associated with higher mortality. We developed a model to predict OS that showed median OS in the low-, intermediate-, and high-risk group, not reached, 32.9 months, and 2.1 months, respectively, P<0.001. We conclude that sequential therapy in elderly patients with active AML demonstrates a strong anti- leukemic effect, and age alone should not be a barrier to this strategy.